1. Field of the Invention
The present invention relates to hydrogels and, more specifically, to hydrogel webs containing silver compounds.
2. Description of the Related Art
Treatment of nosocomial infections costs 11 billion dollars every year in the U.S. alone. About half of these infections are related to medical devices that are implanted in patients for different lengths of duration. It is well documented that the microbes causing device-related infections are attached to surfaces and grow into biofilms, which are highly hydrated structures comprised of a polysaccharide matrix secreted by the bound microbes. Biofilm cells are up to 1000 times more tolerant to antimicrobial agents (hereafter, antimicrobials) and disinfectants than their free-swimming counterparts. Because antibiotics can only eliminate planktonic cells, biofilm-associated infections are normally persistent and associated symptoms reoccur upon the release of cells from biofilms. Clinical cure of device-associated infections requires total removal of the device followed by prolonged antibiotic therapy to effectively clear the infection. With the serious medical consequences of device-associated infections and significant difficulties in treating established biofilms, effective methods for preventing biofilm formation are necessary. Conceptually, the prevention of biofilm formation could be achieved either by covalently modifying the surface with antimicrobials or controlled release of antimicrobials from the surface. Because increasing evidence has shown that medical devices are quickly covered by host proteins once implanted in a human body, materials capable of controlled and sustained release of antimicrobials are highly desired.
Silver, being an antimicrobial agent, has a history in wound healing dating at least two thousand years—since ancient Greece and Rome, owing to its low toxicity to human cells. For example, 16 bacterial species tested, including Escherichia coli, Pseudomonas aeruginosa, and Staphylococcus aureus are inhibited at 1.25 μg/mL silver (Ag+), while 4 μg/mL silver (Ag+) does not exhibit any obvious detrimental effects to mouse bone marrow cells (as a susceptible normal mammalian system). Although modern antimicrobial quickly developed in the last century following the introduction of sulphonamides and penicillin, silver compounds have continued to be attractive as antimicrobial agents due to their unique advantages: (1) a broad spectrum antimicrobial properties against both gram-positive and gram-negative bacteria and (2) existence of multiple cellular targets and therefore less chance for development of resistance in bacteria. For example, silver sulfadiazine (SSD), an antimicrobial agent containing silver nitrate (AgNO3) and a sulphonamide antibiotic, was introduced in 1968. Due to its controllable delivery of silver ions to infected wounds, it has been widely applied to treat infections in burns and scalds. It is believed that the ionic silver (Ag+) released from the dressing has high activity to bind to intracellular proteins and nucleic acids of bacteria, leading to structural changes in bacterial cell membranes. These effects further result in the cellular distortion and loss of viability of the organism. In addition, Ag+ can interact with and denature DNA and RNA, thereby inhibiting cell division and replication. More recently, a variety of silver-based products have been commercialized varying from wound dressing to vascular and urinary catheters. The carrier materials used for silver loading vary from alginates (i.e., Acticoat™, Smith and Nephew and Silvercel, Johnson & Johnson), to hydrogel (i.e., Silvasorb™, Medline), hydrocolloid (i.e., Contreet HTM, Coloplast) and foam (i.e., Contreet FTM, Coloplast). This variety in material form provides wide options in clinical therapy. Recently, the new absorbent non-woven “hydrofiber” dressing, Aquecel Ag™ (Conva Tech), has been introduced. Such non-woven hydrofibers, consisting of sodium carboxymethylcellulose, show apparent advantages of fluid-handling capacity and ease of application and removal.